Molecular genetic studies and delineation of the oculocutaneous albinism phenotype in the Pakistani population

Table 3 Mutations of OCA2 segregating in Pakistani families

Nucleotide change^#	Frequency in control samples	Effect on protein	Location	Family	Ethinicity	Haplotype* S1-S2-S3-S4-S5-S6-S7-S8	Polyphen 2	SNPs3D	Mutation Taster	Allele frequency this study	Regulatory region sequence^¥
Missense
c.954 G > A	0/200	p.Met318Ile	loop TM2-3	PKAB063	Warraich	C-C-C-G-A-T-G-A	Benign	Benign	Polymorphism	7.14%	TAAA TG
c.1456 G > T	0/344	p.Asp486Tyr	within TM7	PKAB052	Lanjay	T-C-T-A-A-C-A-G	Damaging	Damaging	Pathogenic	35.71%	TAAG TG
				PKAB054	Mehay	T-C-T-A-A-C-A-G					TAAG TG
				PKAB055	Mehay	T-C-T-A-A-C-A-G					TAAG TG
				PKAB067	Ghallu	T-C-T-A-A-C-A-G					TAAG TG
				PKAB101	Chaaki	T-C-T-A-A-C-A-G					TAAA TG
c.1580 T > G	0/298	p.Leu527Arg	within TM8	PKAB063	Warraich	C-C-C-G-A-T-G-A				7.14%	TAAA TG
c.2228 C > T		p.Pro743Leu	loop TM12-13	PKAB058	Arain	C-C-T-G-A-C-A-A	Damaging	Damaging	Pathogenic	14.30%	TAAA TG
				PKAB072	Joyia	C-C-T-G-A-C-A-A					TAAA TG
c.2359 G > A		p.Ala787Thr	within TM13	PKAB071	Chohan	C-C-C-G-A-C-G-A	Damaging	Damaging	Pathogenic	7.14%	TAAA TG
Splice site
c.1045-15 T > G	0/364	splicing	within TM3	PKAB060	Bubar	C-C-T-G-A-T-G-A	Damaging	Damaging	Pathogenic	35.71%	TAAA TG
		error^§		PKAB068	Sindhu Jutt	C-C-T-G-A-T-G-A					TAAA TG
				PKAB079	Abbasi	C-C-T-G-A-T-G-A					TAAA TG
				PKAB151	Ansari	T-C-T-G-A-T-G-A					TAAA TG
				PKAB152	Ansari	C-C-T-G-A-T-G-A					TAAA TG

^#Given in bold are the novel variants found in this study. *SNPs used for haplotyping: S1, rs17565841; S2, rs12592307 (p.S788S); S3, rs1800411 (p.C517C); S4, rs1900758; S5, rs1800410; S6, rs10852218; S7, rs1800404; S8, rs12913832. According to Feb. 2009 UCSC Human Genome browser assembly (GRCh37/hg19), the S2 to S6 are present within the coding (S2 and S3) or intronic regions of OCA2. ^§Human Splicing Finder program (http://www.umd.be/HSF/) predicted a cryptic splice donor site 12 nucleotide upstream of known splice acceptor site for exon 9 due to the mutation. ^¥Conserved regulatory element sequence present within intron 86 of the HERC2 gene. N/A not applicable. TM transmembrane domain. TMpred-Prediction of transmembrane regions and orientation (http://www.ch.embnet.org/software/TMPRED_form.html) was used for OCA2 domain prediction.

ISSN: 1750-1172